NSAIAs are used for the relief of signs and symptoms of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. NSAIAs are used alone or as an adjunct in the treatment of biliary colic, fever, and episiotomy pain. It is also used in treatment of gout, acute migraine headaches, and renal colic and in the treatment of postoperative inflammation in patients who have undergone cataract extraction. Aspirin is used for preventing heart and vascular diseases.
Unfortunately, a number of side effects are associated with the use of NSAIAs, most notably GI disturbances such as dyspepsia, gastroduodenal bleeding, gastric ulcerations, and gastritis. Fishman (Fishman; Robert, U.S. Pat. No. 7,052,715) indicated that an additional problem associated with oral medications, is that the concentration levels which must be achieved in the bloodstream must be significant in order to effectively treat distal areas of pain or inflammation. These levels are often much higher than would be necessary if it were possible to accurately target the particular site of pain or injury. Fishman and many others (Van Engelen et al. U.S. Pat. No. 6,416,772; Macrides at al. U.S. Pat. No. 6,346,278; Kirby et al. U.S. Pat. No. 6,444,234, Pearson et al. U.S. Pat. No. 6,528,040, and Botknecht et al. U.S. Pat. No. 5,885,597) have attempted to develop a delivery system for transdermal application by formulation. Song, et al. developed a transdermal drug delivery system for anti-inflammatory analgesic agent comprising of diclofenac diethylammonium salt (Song, et. al., U.S. Pat. No. 6,723,337). Donati, et al. developed a plaster for topical use containing heparin and diclofenac. (Donati, et al., U.S. Pat. No. 6,592,891). Kawaji, et al. developed an oily patch for external use containing diclofenac sodium (Kawaji, at al. U.S. Pat. No. 6,262,121). Effing, et al. developed a device for the transdermal delivery of diclofenac (Effing, et al. U.S. Pat. No. 6,193,996). It is very difficult, however, to deliver therapeutically effective plasma levels of NSAIAs into the host by formulation. Susan Milosovich, et. al. designed and prepared testosteronyl-4-dimethylaminobutyrate.HCl (TSBH), which has a lipophilic portion and a tertiary amine groups that exists in the protonated form at physiological pH. They found that the prodrug (TSBH) diffuses through human skin ˜60 times faster than does the drug (TS) itself [Susan Milosovich, et al., J. Pharm. Sci., 82, 227(1993).